Director, NIMH/NIH/DHHS The National Institute of Mental Health and the American Recovery and Reinvestment Act July 10, 2009 Thomas R. Insel, M.D. Director, NIMH/NIH/DHHS

NIMH Mission To transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

Burden of Disease (DALYs) U.S., Canada, and Western Europe 15-44 years old Source: WHO World Health Report 2002

Public Health Impact: Early Mortality in Individuals with Major Mental Illness (MMI) Average age at time of death : 56 years Increased likelihood of heart disease and suicide Adapted from Colton and Manderscheid, 2006, Prev Chronic Dis

Matching Resources with Public Health Need Direct and indirect components of the economic burden of serious mental disorders, excluding incarceration, homelessness, comorbid conditions and early mortality. ($ in billions) 1992 2002 Health Care Expenditures $62.91 $100.12 Loss of earning $76.71 $193.23 Disability (SSI + SSDI) $16.41 $24.34 Totals $156.0 B $317.6 B Insel, Am J Psychiatry, 2008

Re-Thinking “Mental Illness” Mental disorders are brain disorders. Mental disorders are developmental disorders. Mental disorders result from complex genetic risk plus experiential factors.

Mental Disorders are Brain Disorders Response Pathways for Depression CBT PF MF MCC Cognition (attention-appraisal-action) hc Meds PF P Cg25 PCC BS MEDS PF9/46 PM6 Par40 MCC PCC mF9/10 na-vst thal Mood state Self-awareness insight pACC24 oF11 amg mb-vta Br Med Bul 65:193-207, 2003 Arch Gen Psych 61:34-41-2004 Salience Motivation sACC25 a-ins hth bstem Interoception (drive-autonomic-circadian)

Prolonged Human Brain Development Source: J Giedd, NIMH

A Developmental Brain Model for Schizophrenia Normal Development Possible Paths to Schizophrenia # of Cortical Synapses Psychosis Threshold Intervention 10 15 20 25 Age Based on McGlashan and Hoffman (2000)

Complex Genetics of Mental Illness Penetrance New technology for sequencing Repository of DNA from pts/controls Needed: Funds for supporting large scale effort High Mendelian disease 22q11.2 16p11.1 1q21.1 15q13.3 Disc-1 Intermediate Rare Large effect Modest ANK3 CACNA1C HLA CAM10 Common Small effect Low Frequency of DNA variation in population Very rare Rare Uncommon Common 0.001 0.01 0.10 McCarthy et al., Nat Rev Genetics 2008

NIMH Strategic Plan (4 P’s) Strategic Objective #1: Pathophysiology Strategic Objective #2: Predictive medicine Strategic Objective #3: Preemptive and Personalized Interventions Strategic Objective #4: Public Health Impact – Participatory Research

Nice roadmap but is there any gas in the car?

American Recovery and Reinvestment Act (ARRA)- Impact of Economic Stimulus on NIH

American Recovery and Reinvestment Act (ARRA)- Objectives Stimulate the economy Create and preserve jobs Advance biomedical research $10.4B to NIH $366M to NIMH

Scientific Research Approach - NIMH Stimulate and accelerate biomedical research with existing mechanisms (33%) Funding additional meritorious R01s, R21s and R03s that have been peer reviewed and approved by NIMH Council Administrative supplements to accelerate ongoing research Expand science with new programs (67%) Revisions to extant programs (“Competitive supplements”) New ARRA NIH-wide programs New ARRA IC-specific programs

NIMH ARRA Priorities Jumpstart: the NIMH Strategic Plan (4P’s) the Autism Research Strategic Plan the NIH AIDS Res Strategic Plan Increase training, faculty recruitment, diversity Support beaker-ready projects w 2 year outcomes Process: transparent, careful, accountable

New ARRA NIH-wide Programs Challenge Grants Grand Opportunities (“GO” Grants) Recruit new faculty to conduct research Provide summer jobs for high school / college students and teachers in science labs AREA (R15) Grants } Jumpstart Strategic Plans } Create and Retain Jobs } National effort On average, every NIH grant supports 6 -7 part-time or full-time jobs

Challenge Grants NIMH Challenge Areas: Biomarkers Genomic sequencing 2 year $500k/yr awards – submitted April 27, 2009 Received >21,000 proposals, 894 for NIMH Reviewed June-July, Funded before 9/30/09 NIH OD committed $200M; NIMH has committed $90M NIMH Challenge Areas: Biomarkers Genomic sequencing Schizophrenia interactome AIDS – behavior change Comparative Effectiveness Developing iPS cells

Grand Opportunity Grants 2 year >$500K/yr awards – submitted May 24, 2009 Received 104 proposals for NIMH ($470M) Reviewed June; Funded before 9/30/09 NIMH has committed $67M NIMH GO Grants: Genomic profiling of mental disorders Neurodevelopmental genomics Transcriptional map of developing human brain Clipart images

ARRA NIMH RFA: Research to Address the Heterogeneity of Autism Spectrum Disorders 4 Different mechanisms to address heterogeneity of autism and focus on short-term objectives of IACC Strategic Plan 590 proposals ($500M) submitted May 12; Peer reviewed June 19; Scheduled for Council July 17 Combined commitment is $60M (NIMH, NICHD, NINDS, NIDCR, NIEHS)

Peer Review for ARRA Rapid (initial mail reviews within 1 month) Extensive (364 reviewers for NIMH GO and autism proposals) Careful (Two tier review to ensure quality) Public input (Autism review included consumers)

Transparency: http://www.nih.gov/recovery

Accountability: http://report.nih.gov/

NIMH Signature Project #1 Reducing Suicide in the Army Problem: Suicide rates in Army have doubled Army asked for assistance in assessing risk and resilience in soldiers NIMH commits ARRA funds ($10M) to collaborative effort for historic epidemiological study to follow 15,000 soldiers Study to provide actionable information to Army

NIMH Signature Project #2 Recovery After an Initial Schizophrenic Episode (RAISE) Problem: Schizophrenia associated with chronic disability RAISE will test aggressive, comprehensive treatment (medication, psychosocial, rehabilitation) to optimize outcomes RAISE developed with SSA, SAMHSA, and CMS for “hand off” from research to practice NIMH ARRA funds ($25M) will launch project in 2009

NIMH Signature Project #3 Neurogenomics Problem: Many leads but few genes for psychiatric illnesses (rare variants likely but difficult to detect) New techniques permit rapid, comprehensive sequencing, including detection of rare variants Sequencing is feasible in 2 years NIMH ARRA funds ($20 -30M) will support development of first comprehensive sequencing efforts

NIMH Signature Project #4 Developmental Human Brain Atlas Problem: Absence of a reference atlas for human brain development New techniques permit mapping regional gene expression in the developing human brain Mapping is labor intensive but feasible in 2 years NIMH ARRA funds ($20M) will support development of the digital public resource

NIMH Comparative Effectiveness Research ARRA Projects: Leveraging existing healthcare networks for CER on Mental Disorders and Autism Cost effectiveness of mental health interventions Collaboration with AHRQ CER Program Building ASD registries for use in Comparative Effectiveness Research

What Can We Accomplish With ARRA? Biomedical Progress: Creating a foundation for future progress Creating and Preserving Jobs: >50% of grant budget = personnel Economic Stimulus: Proposals from all 50 states

NIMH ARRA obligations actual and planned for FY2009 (all mechanisms)

Summary ARRA provides an unprecedented opportunity to advance biomedical research while participating in the nation’s economic recovery NIMH is using ARRA funds to jumpstart its strategic plan, support autism and AIDS research, and provide training and faculty positions. Specific signature projects focus on suicide in the Army, schizophrenia, and genomics. Demand for ARRA support high, success relatively low, but ARRA will build foundation for progress.

Paving the Way for Prevention, Recovery, and Cure www.nimh.nih.gov 33

Select NIMH ARRA Funds – 7/10/09 Initiative Committed funding Due Date Proposals received Funding Date Expansion of payline $60M 2008- 2010 ----- 6/09 Supplements $10M adm. $10M comp. 4/09 $205M $ 64M 8/09 Challenge $90M $578M Grand Opportunity $67M 5/09 $470M 9/09 New faculty recruitment $5M $25M Autism RFA $30M $500M 7/09 Army suicide & RAISE $35M 2009

What Happens After ARRA? Demand for research will increase: Success rate (# funded/# proposed) < 10% Many unsuccessful grants return in 2010 Both unsuccessful and successful grants return in 2011 Total # ARRA proposals = 1,703 Estimated success rate in 2011: If 50% return: 13.7% If 75% return: 12.2% If 90% return: 11.5% Required for 20% success rate: 7 -11% increase from FY10 PB